Cell proliferation, differentiation, and survival are often regulated by growth, differentiation, and survival factors, respectively, which are collectively called cytokines. Cytokines bind to their complementary receptors, which transduce the extracellular signal into an intracellular signaling cascade. Fas ligand (FasL) is a cytokine. It is one of the few known cytokines that is a death factor. This ligand binds to its receptor, Fas, a cell-surface protein, and induces apoptosis (cell death). Many tissues and cell lines weakly express Fas, but abundant expression has been found in mouse heart, liver, lung, kidney, ovary and thymus (R. Watanabe-Fukunaga, et al., J. Immunol., 148, 1274-1279 (1992)). In the immune system, Fas and FasL are involved in down-regulation of immune reactions as well as in T cell-mediated cytotoxicity. Malfunction of the Fas system causes lymphoproliferative disorders and accelerates autoimmune diseases, whereas its exacerbation may cause tissue destruction (S. Nagata, et al., Science, 267, 1449-1456 (1995)).
Surprisingly, it has been found that carvedilol, a dual non-selective .beta.-adrenoceptor and .alpha..sub.1 -adrenoceptor antagonist, inhibits the expression of Fas. This inhibition may mean that carvedilol and related Formula I compounds are useful for diseases wherein inhibition of Fas-mediated apoptosis is indicated. Particularly, this inhibition may mean that carvedilol and related Formula I compounds are useful for blocking ischemia-induced apoptosis in cardiac cells, for preventing or inhibiting tissue remodeling, in particular in cardiac tissue and blood vessels, for treating autoimmune diseases, and for inhibiting tumor growth and metastasis.